Follow-up of a patient with CERNUNNOS deficiency

1
Follow-up of a patient with CERNUNNOS deficiency

• Edyta Heropolitanska-Pliszka
• Immunology Department
• Childrens Memorial Health Institute Warsaw,
  Poland

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CERNUNNOS / XLF

• a new type of radiosensitive
• T-B-NK SCID

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Cernunnos deficiency core components

• consanguinity
• recurrent bacterial and opportunistic infections
• microcephaly
• severe growth retardation
• dysmorfic features
• hypogammaglobulinemia IgG and IgA
• fluctuating level of IgM
• mild to severe B and T lymphopenia, NK cells not
  affected
• all T cells of memory phenotype (CD45 RO)
• impaired response of T cells to PHA
• chromosomal translocations in lymphocytes
• increased radiosensitivity

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8-year-old boy

• irrelevant family history
• recurrent bacterial and viral infections of upper
  and lower respiratory tract since infancy period
  (otitis, bronchitis and pneumonitis every 2
  months)
• significant microcephaly (-5 SD)
• birdlike face
• growth retardation (lt3 pc)

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Immunologic investigation

• IgG 120-530 mg/dl,
• IgA 6-18 mg/dl,
• IgM 921-1390 mg/dl
• CD19 4,3 - 81 cells/ul
• CD3 32 - 380 cells/ul
• CD1656 43 - 665 cells/ul
• CD4 CD45RO 91,8 - 600 cells/ul
• CD8 CD45RO 64.7 - 466 cells/ul
• PHA 2635/-7
• anty-CD3 838/-65
• spontaneous chromosomal fragility
• increased radiosensitivity of patients
  fibroblasts

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CERNUNNOS deficiency

• homozygous
• stop codon mutation
• Y167X

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HSCT

• March 2006 - MUD PBPC
  (CD34 12,7x106/kg b.m)
• Conditioning regimen reduced because of breakage
  of chromosomes (FluCyATG)
• Early outcome
• 12 day - GVHD II stage in skin (steroids)
• 17 day - good haematological reconstitution
• 27 day - complete chimerism

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62 day

• good clinical condition, no symptoms of
  infection
• complete chimerism, no signs of GVHD
• immunosupression CsA and steroids (Encorton 0,5
  mg/kg b.m.)
• prophylaxis Co-trimoxazole, Azithromycin,
  Acyclovir, Fluconazole

9
155 day

• hemorrhagic cystitis of unknown origin (polioma-,
  adeno-, CMV, EBV excluded)
• treatment forced diuresis, IVIG substitution,
  intravenous Acyclovir
• 210 day good clinical condition, normal blood
  and urine tests, complete chimerism

10
385 day

• Protracted fever with lymphadenopathy, skin
  changes (chronic GVHD)
• CMV PCR (-)
• Aspergillus ELISA 0,452 PCR (-)
• Cryptosporidium sp. PCR (-)
• EBV DNA 140-560 copies
• Diagnosis EBV infection
• Treatment Azithromycin, Co-trimoxazol,
  Acyclovir, Worikonazol, IVIG every 10 days, UDCA,
  Gancyclovir

• WBC 7,8 K/ul
• N-29 L-35
• E-27 AL-2
• M-7
• Hgb 10,2 g/dl
• Plt - 135 K/ul
• GOT 110 U/l
• GGTP 335 U/l
• CRP - 1,2 mg/dl
• LDH 245 U/l

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425 day - last follow-up

• IgG 590 mg/dl,
• IgA 41 mg/dl,
• IgM 60 mg/dl
• CD19 12,3 - 405 cells/ul
• CD3 69 - 2310 cells/ul
• CD1656 13 - 469 cells/ul
• Alone 337/-80
• PHA 16871/-645
• CD3 16199/-125
• Complete chimerism

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Thank you for attention